FDA Requests Additional Manufacturing Information for High-Dose Spinraza, Biogen Plans Prompt Resubmission

The U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) to Biogen regarding its application for a high-dose regimen of Spinraza (nusinersen) in the treatment of spinal muscular atrophy (SMA). The agency has requested updated technical information related to the chemistry, manufacturing, and controls (CMC) portion of the filing.

Biogen's Response and Resubmission Plans

Biogen expressed surprise at the FDA's decision but remains committed to bringing the high-dose regimen to SMA patients. Dr. Priya Singhal, head of development at Biogen, stated, "While this outcome was unexpected, we remain committed to bringing the high dose regimen to people living with SMA. We are working diligently to provide the necessary information to the FDA."

The company emphasized that the FDA's rejection did not cite any issues with the clinical data supporting the high-dose regimen. Biogen plans to resubmit its application "promptly" and noted that the FDA has provided options for resolving the technical information concerns.

High-Dose Spinraza: Dosing and Clinical Data

The proposed high-dose regimen for Spinraza involves two 50-mg starter doses given 14 days apart, followed by a 28-mg maintenance dose administered monthly. This differs from the currently approved regimen, which consists of three 12-mg starter doses given two weeks apart, a fourth 12-mg dose a month later, and then 12-mg maintenance doses every four months.

Biogen's decision to pursue the high-dose option was based on positive results from its phase 2/3 Devote trial. The Part B portion of the study demonstrated significant improvements in SMA patients' mobility, as measured by the Children's Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTED). The company has also released data suggesting that higher-dose Spinraza could benefit a range of SMA patients, including those who haven't been treated previously and those with early- and late-onset disease.

Regulatory Status and Industry Context

While the FDA has requested additional information, Biogen has already secured approval for the high-dose Spinraza regimen in Japan. The European Medicines Agency is currently reviewing the company's application.

The Spinraza setback comes alongside another SMA-related rejection from the FDA. Scholar Rock announced that the agency had turned down the application for its SMA candidate apitegromab due to manufacturing site inspection findings. The facility in question, previously owned by Catalent and now part of Novo Nordisk, has been implicated in multiple FDA rejections in recent months.

As Biogen works to address the FDA's concerns, industry analysts remain optimistic about the eventual approval of high-dose Spinraza. The company's swift response and the absence of clinical data issues suggest that this setback may be a manageable delay in bringing an improved treatment option to SMA patients.